Crosstalk between mesangial and endothelial cells:: Angiotensin II down-regulates endothelin-converting enzyme 1

Objective: Since mesangial and endothelial cells interact in the kidney, the present experiments were designed to analyze the ability of human mesangial cells ( HMC) to modulate endothelin- 1 ( ET- 1) synthesis by human umbilical vein endothelial cells ( HuVEC). Methods and Results: The supernatants of HuVEC/ HMC contained significantly lower amounts of ET- 1 than those of HuVEC alone. This effect was not due to a decreased prepro- ET- 1 mRNA expression and was only partially the consequence of HMC-dependent ET- 1 degradation. Therefore, we tested the influence of the coculture on endothelin- converting enzyme- 1 ( ECE- 1), and found a significant reduction of its mRNA and protein levels as well as a decreased activity in HuVEC/ HMC as compared to HuVEC alone. Using a pharmacological blockade approach ( sulotrobam, BN52021, losartan or catalase), losartan was shown to completely abolish down- regulation of ECE- 1 observed in HuVEC/ HMC. Angiotensin II ( AII) induced a dose and time- dependent inhibition of ECE- 1 expression in HuVEC. Conclusions: These results support the importance of cross- talk among different cell types in the regulation of vascular or renal function. ET- 1, and particularly ECE- 1, might constitute a target in this regulation. In addition, locally synthesized AII could be one of the mediators involved in the down- regulation of ECE- 1. Copyright (C) 2005 S. Karger AG, Basel.